Dans le cadre du dernier congrès « Le Printemps de la Cardiologie » qui a eu lieu à Bordeaux en avril dernier, un doctorant du laboratoire, Adrien Kleindienst, a reçu le prix du meilleur poster pour la session scientifique « hypoxie myocardique, reperfusion, accident vasculaire cérébral » qui comportait plus de 30 communications au total.
Félicitations pour son travail !
Résumé du travail :
Exercise training protects the heart against ischemia reperfusion in a mice model of diet-induced metabolic syndrome: no implication of the classic β3 adrenergic receptors – eNOS pathway.
Kleindienst A1, Battault S1, Rosselin M3, Meyer G1, Gayrard S1, Riva C1, Geny B4, Durand G3, Cazorla O2, Reboul C1
1, Laboratoire de Pharm-écologie cardiovasculaire (EA4278), Université d’ Avignon, 74 rue Louis Pasteur 84000-Avignon- France.
2, UMR1046 INSERM CNRS, Université de Montpellier. Montpellier.
3, UMR CNRS 5247 Institut des biomolécules Max Mousseron, Montpellier
4, EA 3072, Fédération de MédecineTranslationelle, Faculté de Médecine, Université de Strasbourg
Metabolic syndrome is associated with a higher cardiac vulnerability to ischemia-reperfusion (IR). Regular exercise is recognized to protect the heart. This has been recently attributed to β3-adrenergic receptors (β3-AR) stimulation and subsequent increase in endothelial nitric oxide synthase (eNOS) activation. However, the role of this pathway in exercise-induced cardioprotection in animals with metabolic syndrome is unknown. We thus evaluated the role of the β3-AR/eNOS pathway in exercise-induced cardioprotection in a mouse model of metabolic syndrome. C57Bl6 mice were fed with high fat and sucrose diet (HFS) for 12 weeks and some had treadmill-exercise with a moderate intensity the last 4 weeks (HFS-Ex). First, HFS hearts were more sensitive to IR, which was prevented by exercise. Even though exercise protects the HFS heart, this was not associated with increased activation state of eNOS (level of eNOS-Pser1177 and the dimer/monomer ratio). Consequently, no increase in NO metabolites storage was observed after exercise in HFS hearts. This result may be explained by the loss of the β3-AR-eNOS pathway in HFS hearts. Indeed, the use of BRL37344, an agonist of β3-AR, increased eNOS-Pser1177 and protected the heart of Ctrl mice, whereas it had no effect in HFS hearts. Finally, considering that exercise-induced cardioprotection is also classically associated with increased antioxidant status, we next evaluated ROS production during early reperfusion and the subsequent activation of the apoptosis end-effector caspase 3. At early reperfusion we found that HFS increased ROS and caspase 3 activation. This phenomenon was blunted in HFS-Ex. Finally, a treatment with LPBNAH, a more amphiphilic nitrone antioxidant derived from PBN normalized HFS heart vulnerability to IR. To conclude these results showed that exercise-induced cardioprotection in HFS hearts is independent of the classical β3-AR-eNOS pathway, but involved oxidative stress during IR.